CN108884074B - Herbicidal pyridazinone compounds - Google Patents

Herbicidal pyridazinone compounds Download PDF

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CN108884074B
CN108884074B CN201780023236.9A CN201780023236A CN108884074B CN 108884074 B CN108884074 B CN 108884074B CN 201780023236 A CN201780023236 A CN 201780023236A CN 108884074 B CN108884074 B CN 108884074B
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compound
formula
methyl
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oxo
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CN108884074A (en
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P·M·伯顿
S·高利尔
P·R·泽帕
M·J·沃金斯
M·B·阿斯皮纳尔
E·J·埃梅特
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Syngenta Participations AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D237/14—Oxygen atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/58—1,2-Diazines; Hydrogenated 1,2-diazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Abstract

The present invention relates to compounds having formula (I),
Figure DDA0001826282020000011
or an agronomically acceptable salt of said compound, wherein A1、R1、Ra、Rb、RcAnd RdAs defined herein. The invention further relates to herbicidal compositions comprising compounds of formula (I), to intermediate compounds for the production of compounds of formula (I), to methods for the production of compounds of formula (I) and to the use of compounds of formula (I) for controlling weeds, in particular in crops of useful plants.

Description

Herbicidal pyridazinone compounds
The present invention relates to novel herbicidal compounds, to processes for preparing them, to herbicidal compositions comprising these novel compounds, and to their use for controlling weeds, in particular in crops of useful plants, or for inhibiting plant growth.
Herbicidal pyridazinone compounds are disclosed in WO 2012/136703. These compounds were shown to provide effective weed control for a variety of problematic weed species. The present invention relates to novel herbicidal pyridazinone compounds which exhibit additional improved properties. In particular, the compounds of the present invention exhibit improved crop selectivity. That is, they continue to provide effective levels of weed control while exhibiting a reduction in undesirable crop phytotoxicity.
Thus, according to the present invention there is provided a compound having the formula (I):
Figure BDA0001826282010000011
or an agronomically acceptable salt thereof, or a pharmaceutically acceptable salt thereof,
wherein
R1Selected from the group consisting of: hydrogen, halogen, cyano, nitro, C1-C6Alkyl-, C3-C6cycloalkyl-C2-C6-alkenyl-, C2-C6Alkynyl-, C1-C6Haloalkyl-, C1-C6alkoxy-C1-C3Haloalkoxy-, C1-C6alkoxy-C1-C3Alkyl-, C1-C6alkyl-S (O) p-and C1-C6haloalkyl-S (O) p-;
A1selected from the group consisting of: o, C (O) and (CR)eRf)；
Ra、Rb、Rc、Rd、ReAnd RfEach independently selected from the group consisting of: hydrogen and C1-C4Alkyl-, wherein RaAnd RcMay be taken together to form C1-C3An alkylene chain; and is
p is 0, 1 or 2.
C1-C6Alkyl-and C1-C4Alkyl radicalIncluding, for example, methyl (Me, CH)3) Ethyl (Et, C)2H5) N-propyl (n-Pr), isopropyl (i-Pr), n-butyl (n-Bu), isobutyl (i-Bu), sec-butyl and tert-butyl (t-Bu).
C2-C6-alkenyl-includes, for example, -CH ═ CH2(vinyl) and-CH2-CH＝CH2(propenyl group).
C2-C6Alkynyl-includes, for example, -C.ident.CH (ethynyl) and-CH2-C ≡ CH (propargyl).
Halogen (or halo) includes, for example, fluoro, chloro, bromo or iodo. The same correspondingly applies to halogen in the context of the other definitions, for example haloalkyl.
C1-C6Haloalkyl-includes, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2, 2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1-difluoro-2, 2, 2-trichloroethyl, 2,2,3, 3-tetrafluoropropyl and 2,2, 2-trichloroethyl, heptafluoro-n-propyl and perfluoro-n-hexyl.
C1-C6Alkoxy-includes, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy or pentoxy or hexoxy isomers, preferably methoxy and ethoxy.
C1-C3Haloalkoxy-includes, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2, 2-trifluoroethoxy, 1,2, 2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2, 2-difluoroethoxy or 2,2, 2-trichloroethoxy, preferably difluoromethoxy, 2-chloroethoxy or trifluoromethoxy.
C1-C6alkyl-S- (alkylthio) includes, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio. C1-C6haloalkyl-S- (haloalkylthio) relates to halogenated derivatives thereof.
C1-C6Alkyl-s (o) - (alkylsulfinyl) includes, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl, preferably methylsulfinyl or ethylsulfinyl. C1-C6Haloalkyl-s (o) - (haloalkylsulfinyl) relates to halogenated derivatives thereof.
C1-C6alkyl-S (O)2- (alkylsulfonyl) includes, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl, preferably methylsulfonyl or ethylsulfonyl. C1-C6haloalkyl-S (O)2- (haloalkylsulfonyl) relates to halogenated derivatives thereof.
C1-C6alkoxy-C1-C3Alkyl-includes, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n-propoxymethyl, n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.
C3-C6Cycloalkyl-includes, for example, cyclopropyl (c-propyl (c-Pr)), cyclobutyl (c-butyl (c-Bu)), cyclopentyl (c-pentyl), and cyclohexyl (c-hexyl).
In a preferred embodiment of the present invention, there is provided a compound having formula (I), wherein R1Is C1-C6Alkyl- (preferably methyl) or C3-C6Cycloalkyl- (preferably cyclopropyl). In a more preferred embodiment, R1Is methyl or cyclopropyl.
In a preferred embodiment of the present invention, there is provided a compound having formula (I), wherein a1Is CReRfAnd R iseAnd RfIs hydrogen.
In another preferred embodiment of the present invention, there are provided compounds having formula (I), wherein a1Is CReRfAnd R isa、Rb、Rc、Rd、ReAnd RfIs hydrogen.
In another preferred embodiment of the present invention, there are provided compounds having formula (I), wherein a1Is CReRf；Ra、Rb、Rc、RdAnd ReIs hydrogen and RfIs methyl.
In another preferred embodiment of the present invention, there are provided compounds having formula (I), wherein a1Is CReRf；Ra、Rb、Rc、RdIs hydrogen and ReAnd RfIs methyl.
In another preferred embodiment of the present invention, there are provided compounds having formula (I), wherein a1Is CReRf；Rb、Rd、ReAnd RfIs hydrogen, and RaAnd RcTogether forming a vinyl group (-CH)2-CH2-) chain.
In another preferred embodiment of the present invention, there are provided compounds having formula (I), wherein a1Is C ═ O and Ra、Rb、RcAnd RdIs methyl.
In another preferred embodiment of the present invention, there are provided compounds having formula (I), wherein a1Is O and Ra、Rb、RcAnd RdIs methyl.
The compounds of formula (I) may contain asymmetric centers and may exist as a single enantiomer, in any proportion of enantiomeric pair, or wherein more than one asymmetric center is present, containing all possible ratios of diastereomers. Typically, one of these enantiomers has enhanced biological activity compared to the other possibilities.
Similarly, where disubstituted or trisubstituted olefins are present, these may be present in the E or Z form or as a mixture of the two in any proportion.
Furthermore, the compounds of formula (I) may be in equilibrium with alternative tautomeric forms. Thus, compounds having formula (I) are also described in the keto form, but they may also be in the alternative enol form, as described in formula (I') below.
Figure BDA0001826282010000041
All tautomeric forms (single tautomers or mixtures thereof), racemic mixtures and single isomers are included within the scope of the invention.
Table C1-examples of herbicidal compounds of the present invention.
Figure BDA0001826282010000042
Figure BDA0001826282010000051
Figure BDA0001826282010000061
Figure BDA0001826282010000071
The invention also provides agriculturally acceptable salts of compounds having formula (I). Preferably, the compound having formula (I) is a salt that can be formed with: amines, including primary, secondary and tertiary amines (e.g., ammonia, dimethylamine and triethylamine), alkali metal and alkaline earth metal bases, transition metal or quaternary ammonium bases. Particular preference is given to aluminum, calcium, cobalt, copper (I), copper (II)), iron (II), iron (III)), magnesium, potassium, sodium or zinc salts of compounds of the formula (I); copper, potassium and sodium are particularly preferred.
The compounds of formula (I) according to the invention can be used as herbicides by themselves, but they are usually formulated into herbicidal compositions using co-formulations such as carriers, solvents, Surfactants (SAA) and adjuvants. Accordingly, the present invention further provides a herbicidal composition comprising a herbicidal compound according to any one of the preceding claims and an agriculturally acceptable co-formulation. The composition may be in the form of a concentrate which is diluted prior to use, although ready-to-use compositions may also be prepared. The final dilution is usually done with water, but for example liquid fertilizers, micronutrients, biological organisms, oils or solvents may be used instead of or in addition to water.
The herbicidal compositions generally comprise from 0.1 to 99% by weight, especially from 0.1 to 95% by weight, of a compound of formula I and from 1 to 99.9% by weight of a co-formulation, which preferably comprises from 0 to 25% by weight of a surface-active substance.
The composition may be selected from a number of formulation types. These include Emulsion Concentrates (EC), Suspension Concentrates (SC), Suspoemulsions (SE), Capsule Suspensions (CS), water dispersible granules (WG), Emulsifiable Granules (EG), water-in-oil Emulsions (EO), oil-in-water Emulsions (EW), Microemulsions (ME), Oil Dispersions (OD), oil suspensions (OF), oil soluble liquids (OL), soluble concentrates (SL), ultra low volume Suspensions (SU), ultra low volume liquids (UL), masterbatches (TK), Dispersible Concentrates (DC), Soluble Powders (SP), Wettable Powders (WP), ZC (combination OF SC and CS) and Soluble Granules (SG). In any event, the type of formulation chosen will depend on the particular purpose envisaged and the physical, chemical and biological characteristics of the compound of formula (I) and any additional ingredients.
Soluble Powders (SP) may be prepared by mixing a compound of formula (I) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as polysaccharides) and optionally one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture was then ground to a fine powder. Similar compositions can also be granulated to form water-Soluble Granules (SG).
Wettable Powders (WP) may be prepared by mixing a compound of formula (I) with one or more solid diluents or carriers, one or more wetting agents and preferably, one or more dispersing agents, and optionally, one or more suspending agents to facilitate dispersion in a liquid. The mixture was then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).
Granules (GR) may be formed in this way: formed by granulating a mixture of a compound of formula (I) with one or more powdered solid diluents or carriers, or preformed blank particles by absorbing a compound of formula (I) (or a solution thereof in a suitable agent) into a porous particulate material (such as pumice, attapulgite clay, fuller's earth, kieselguhr, diatomaceous earth (Diatomaceous earth) or corncob meal) or by adsorbing a compound of formula (I) (or a solution thereof in a suitable agent) onto a hard core material (such as sand, silicates, inorganic carbonates, sulphates or phosphates) and, if necessary, drying. Agents commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones, and esters) and stickers (such as polyvinyl acetate, polyvinyl alcohol, dextrin, sugars, and vegetable oils). One or more other additives (e.g., emulsifying, wetting or dispersing agents) may also be included in these granules.
Dispersible Concentrates (DC) may be prepared by dissolving a compound of formula (I) in water or an organic solvent such as a ketone, alcohol or glycol ether. These solutions may contain surfactants (e.g. to improve water dilution or to prevent crystallization in the spray tank).
Emulsifiable Concentrates (EC) or oil-in-water Emulsions (EW) may be prepared by dissolving a compound of formula (I) in an organic solvent, optionally comprising one or more wetting agents, one or more emulsifying agents or a mixture of said agents. Suitable organic solvents for use in EC include aromatic hydrocarbons (e.g. alkylbenzenes or alkylnaphthalenes, such as SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a registered trademark), ketones (e.g. cyclic rings)Hexanone or methylcyclohexanone) and alcohols (e.g., benzyl alcohol, furfuryl alcohol or butanol), and dimethylamides of fatty acids (e.g., C8-C10Fatty acid dimethylamide). The EC product may spontaneously emulsify upon addition to water, resulting in an emulsion with sufficient stability to allow spray application through appropriate equipment.
Preparation of an EW involves obtaining a compound of formula (I) as a liquid (which may melt at a reasonable temperature, typically below 70 ℃, if it is not liquid at room temperature) or in solution (by dissolving it in a suitable solvent), and then emulsifying the resulting liquid or solution into water containing one or more SAAs under high shear to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, aromatic solvents such as alkylbenzenes or alkylnaphthalenes, and other suitable organic solvents that have low solubility in water.
Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents and one or more SAAs to spontaneously produce thermodynamically stable isotropic liquid formulations. The compound of formula (I) is initially present in water or in a solvent/SAA blend. Suitable solvents for use in ME include those described hereinbefore for use in EC or EW. The ME may be an oil-in-water system or a water-in-oil system (which system is present can be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. ME is suitable for dilution into water while remaining as a microemulsion or forming a conventional oil-in-water emulsion.
Suspension Concentrates (SC) may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of formula (I). The SC may be prepared by ball or bead milling a solid compound of formula (I) in a suitable medium, optionally using one or more dispersants, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition, and a suspending agent may be included to reduce the rate of sedimentation of the particles. Alternatively, the compound of formula (I) may be dry milled and added to water containing the reagents described hereinbefore to produce the desired end product.
Aerosol formulations include a compound having formula (I) and a suitable propellant (e.g., n-butane). The compound of formula (I) may also be dissolved or dispersed in a suitable medium (e.g. water or a water-miscible liquid such as n-propanol) to provide a composition for use in a non-pressurised manual spray pump.
Capsule Suspensions (CS) can be prepared in a similar manner to the preparation of EW formulations, but with an additional polymerization stage such that an aqueous dispersion of oil droplets is obtained, each of which is surrounded by a polymeric shell and contains a compound of formula (I) and optionally a carrier or diluent therefor. The polymer shell may be prepared by an interfacial polycondensation reaction or by a coacervation procedure. These compositions can provide controlled release of the compounds having formula (I). The compounds of formula (I) may also be formulated in a biodegradable polymer matrix to provide slow controlled release of the compound.
Soluble concentrates (SL) may be prepared by dissolving the active ingredient in an aqueous liquid optionally containing one or more wetting agents and/or one or more buffering agents.
The composition may include one or more additives to improve the biological properties of the composition, for example by improving wetting, retention or distribution on a surface; rain protection on the surface being treated; or absorption or flow of a compound having formula (I). Such additives include Surfactants (SAA), oil-based spray additives, for example certain mineral or natural vegetable oils (such as soybean and rapeseed oil), modified vegetable oils (such as methylated rapeseed oil (MRSO)) and blends of these with other bioaugmentation adjuvants (ingredients that can aid or modify the action of the compounds of formula (I)).
Examples of co-formulations include: -
The wetting, dispersing and emulsifying agents may be SAA of the cationic, anionic, amphoteric or non-ionic type.
Suitable cationic types of SAA include quaternary ammonium compounds (e.g. cetyltrimethylammonium bromide), imidazolines, and amine salts.
Suitable anionic SAAs include alkali metal salts of fatty acids, salts of aliphatic monoesters of sulfuric acid (e.g., sodium lauryl sulfate), salts of sulfonated aromatic compounds (e.g., sodium dodecylbenzenesulfonate, calcium dodecylbenzenesulfonate, butylnaphthalenesulfonate, and mixtures of sodium di-isopropyl-naphthalenesulfonate and sodium tri-isopropyl-naphthalenesulfonate), ether sulfates, alcohol ether sulfates (e.g., sodium laureth-3-sulfate), ether carboxylates (e.g., sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (primarily monoesters) or with phosphorus pentoxide (primarily diesters), e.g., the reaction between lauryl alcohol and tetraphosphoric acid; alternatively these products may be ethoxylated), sulfosuccinamates, paraffin or olefin sulfonates, salts of sulfuric acid, salts of sulfonated aromatic compounds (e.g., sodium laureth-3-sulfate), ether sulfates, alcohol ether sulfates (e.g, Taurates, lignosulfonates, and phosphate/sulfate esters of tristyrylphenol.
Suitable amphoteric SAAs include betaines, propionates and glycinates.
Suitable non-ionic types of SAA include condensation products of alkylene oxides (e.g., ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof) with fatty alcohols (e.g., oleyl alcohol or cetyl alcohol); partial esters from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (containing ethylene oxide and propylene oxide); an alkanolamide; monoesters (e.g., fatty acid polyethylene glycol esters); amine oxides (such as lauryl dimethyl amine oxide); lecithin and sorbitan and its esters, alkyl polyglycosides and tristyrylphenols.
Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swellable clays (such as bentonite or attapulgite).
The compositions of the present invention may further comprise one or more additional pesticides. For example, the compounds according to the invention can also be used in combination with other herbicides or plant growth regulators. Thus, in a preferred embodiment, herbicidal compositions are provided comprising (a) a compound having formula (I) and (B) one or more herbicides selected from the group consisting of: acetochlor, acifluorfen (sodium acifluorfen), aclonifen, alachlor, diclofen, ametryn, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminopyralid, fentrazone, sulbenfop, atrazine, beflubutamid, flumethan, flumetsulam, bensulfuron-methyl (including bensulfuron-methyl), bentazone, dicyclopyrone, clofenpyr, bispyribac sodium, bromacil, bromoxynil, butachlor, butafenacet, butafenacil, carfentrazone-ethyl (including carfentrazone-ethyl), cloransulam, chlorimuron (including chlorimuron-ethyl), chlorotoluron, chlorsulfuron, cinosulfuron, triasulfuron, indolone (including indolone-methyl), clethodim, clodinafop (including clodinafop-propargyl), clomazone, clopyralid, thiazopyr, carfentrazone (including cyhalofop-butyl), cyhalofop-butyl, 2,4-D (including choline and 2-ethylhexyl esters thereof), ethameturon, desmedipham, dicamba (including aluminum, aminopropyl, di-aminopropylmethyl, choline, dichlorprop-p-ropionic acid, diglycolamine, dimethylamine, potassium and sodium salts thereof), diclofop-methyl (including diclofop-methyl), diclosulam, difenzoquat, diflufenican, diflufenzopyr, dimethenamid, diquat dibromide, diuron, EPTC, penoxsulam, ethametsulfuron, furbenfural, fenoxaprop-ethyl (including fenoxaprop-ethyl), fequinar, flazasulfuron, florasulam, oxaflorfenin (including oxaflorfenin-butyl), fluorone (including sodium fluorone), fluthiacet, flumetsulam, flumeturon, fluumeton, fluorometuron, fluoroglycofen-ethyl, fluridone, flufenoxaprop-ethyl, flufenoxaprop-p-ethyl, flufenoxaprop-ethyl, Flumioxazin, flazasulfuron (including fluazisulfuron-methyl sodium), fluroxypyr (including fluroxypyr), flurtamone, metribuzin (including fluazifop methyl), fomesafen, foramsulfuron, glufosinate (including ammonium salts thereof), glyphosate (including hydrazine, isopropylammonium and potassium salts thereof), halauxifen (including halauxifen-methyl), halosulfuron (including halosulfuron-methyl), haloxyfop (including haloxyfop), hexazinone, imazac, imazapic, imazapyr, imazaquin, imazethapyr, imazapyr, imazachlor, iodometsulfuron (including methyl iodometsulfuron methyl sodium), iofensulfuron (including iofensulfuron sodium), iobennitrile, ipncarbazone, isoproturon, isoxaflutole, isoxaflutolone, lactofen, linuron, pa, homofenoxuron 4-methyl chloride, metoclopramide, metolachlor, Mefenacet, mesosulfuron (including mesosulfuron-methyl), mesotrione, metamitron, metazachlor, xosulfuron, metolachlor, metoxuron, metribuzin, metsulfuron-methyl, bensulfuron-methyl, napropamide, alachlor, nicosulfuron, norflurazon, orthosulfamuron, oxadiargyl, oxadiazon, epoxysulfuron, oxaziclomefone, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, dimethenamid, picloram, fluazinam, pinoxaden, propafen, prodiamine, prometryn, propyzan, bensulfuron-methyl, prosulfuron, pyrazosulfuron-ethyl, pyrisulfuron-methyl, pyriminostrobin-ethyl, pyriminostrobin-methyl, pyriminon-ethyl, pyriminon-methyl, pyrimethanil, bensulfuron-methyl, bensulfuron-ethyl, pyrifturon, pyribensulfuron-methyl, pyri, Pyridate, pyrithiobac-methyl, pyrithiobac-sodium, rochlor sulfone, pyroxsulam, quinclorac, quizalofop-p-ethyl (including quizalofop-p-ethyl), rimsulfuron, pyribenzoxim, sethoxydim, simetryn, S-metolachlor, sulcotrione, sulfentrazone, sulfosulfuron (including sulfometuron), sulfosulfuron, buthiuron, trizanone, tembotrione, pyroxene, terbuthylazine, desmetryn, thiencarbazone, thifensulfuron, diphenoxylate, topirimate, tralkoxydim, triafamone, triallate, triasulfuron, tribenuron-methyl (including tribenuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), trifluralin, triflusulfuron, 4-amino-3-chloro-6- (4-chloro-2-fluoro-3-methoxyphenyl) -5-fluoropyridin-2-fluoro pyridine-sodium -carboxylic acid ester (compound B1), 4-hydroxy-1-methoxy-5-methyl-3- [4- (trifluoromethyl) -2-pyridinyl ] imidazolidin-2-one (compound B2), 4-hydroxy-1, 5-dimethyl-3- [4- (trifluoromethyl) -2-pyridinyl ] imidazolidin-2-one (compound B3), 5-ethoxy-4-hydroxy-1-methyl-3- [4- (trifluoromethyl) -2-pyridinyl ] imidazolidin-2-one (compound B4), 4-hydroxy-1-methyl-3- [4- (trifluoromethyl) -2-pyridinyl ] imidazolidin-2-one (compound B5), 4-hydroxy-1, 5-dimethyl-3- [ 1-methyl-5- (trifluoromethyl) pyrazol-3-yl ] imidazolidin-2-one (compound B6), (4R)1- (5-tert-butylisoxazol-3-yl) -4-ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one (compound B7), a compound having the formula B8,
Figure BDA0001826282010000131
wherein the content of the first and second substances,
R1is H, C1-C6Alkyl radical, C1-C6Haloalkyl or C4-C8A cycloalkyl group;
R6is H, C1-C6Alkyl, or C1-C6An alkoxy group;
Q1is an optionally substituted ring system selected from the group consisting of: phenyl, thienyl, pyridyl, benzodioxolyl, naphthyl, benzofuranyl, furanyl, benzothiophenyl, and pyrazolyl, wherein when said ring system is substituted 1 to 3R4When substituted;
Q2is an optionally substituted ring system selected from the group consisting of: phenyl, pyridyl, benzodioxolyl, pyridonyl, thiadiazolyl, thiazolyl, and oxazolyl, wherein when said ring system is substituted with 1 to 3R5When substituted;
each R4Independently of one another is halogen, C1-C6Alkyl radical, C1-C6Haloalkyl, C1-C6Alkoxy radical, C1-C6Haloalkoxy, C3-C8Cycloalkyl, cyano, C1-C6Alkylthio radical, C1-C6Alkylsulfinyl radical, C1-C6Alkylsulfonyl group, SF5、NHR8Optionally substituted with 1-3R7Substituted phenyl, or optionally substituted with 1-3R7A substituted pyrazolyl group;
each R5Independently of one another is halogen, C1-C6Alkyl radical、C1-C6Haloalkyl, C1-C6Alkoxy radical, C1-C6Haloalkoxy, cyano, nitro, C1-C6Alkylthio radical, C1-C6Alkylsulfinyl, or C1-C6An alkylsulfonyl group;
each R7Independently is C1-C6Alkyl, halogen, or C1-C6A haloalkyl group; and is
R8Is C1-C4An alkoxycarbonyl group;
and a compound having the formula B9,
Figure BDA0001826282010000141
wherein the content of the first and second substances,
R11is H, C1-C6Alkyl radical, C1-C6Haloalkyl or C4-C8A cycloalkyl group;
n is an integer of 0, 1,2 or 3;
p is an integer of 0, 1,2 or 3;
each R2Independently of one another is halogen, C1-C6Haloalkyl, or C1-C6A haloalkoxy group; and is
Each R3Independently of one another is halogen, C1-C6Haloalkyl, C1-C6A haloalkoxy group.
More preferably, (B) is one or more herbicides selected from the group consisting of: acetochlor, alachlor, ametryn, amicarbazone, atrazine, dicyclopyrone, bromoxynil, butachlor, chlortoluron, clodinafop-propargyl, clopyralid, 2,4-D (including choline salt and 2-ethylhexyl ester thereof), dicamba (including aluminum, aminopropyl, bisaminopropylmethyl, choline salt, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salt thereof), diflufenican, dimethenamid, diuron, haloxyfop-methyl, phenyzine, florasulam, fluazifop-methyl, fluroxypyr, flosulam sodium, fluthiacet-methyl, foramsulfuron, glufosinate (including ammonium salt thereof), fomesafen, glyphosate (including diammonium, isopropylammonium and potassium salt thereof), halauxifen-methyl, iodosulfuron methyl, isoxaflutole, isoproturon, methabenzuron, clorac-methyl, clorac-propargyl, and clorac-methyl, Linuron, MCPA, homo2-methyl chloropropionic acid, mesosulfuron-methyl, mesotrione, pyrazoxam, S-metolachlor, metribuzin, metsulfuron-methyl, nicosulfuron, pendimethalin, dimethenamid, pinoxaden, prometryn, prosulfocarb, prosulfuron, pyrasulfozole, pyridate, rochlorsulone, pyroxsulam, rimsulfuron, simazine, sulcotrione, sulfentrazone, tembotrione, terbutryn, thiencarbazone, topirit, topramezone, triasulfuron and trifluoxazine.
Even more preferably, (B) is one or more herbicides selected from the group consisting of: atrazine, dicyclopyrone, bromoxynil, clodinafop-propargyl, diflufenican, fenoxaprop-ethyl, florasulam, flufenacet, fluroxypyr, glufosinate (including its ammonium salt), glyphosate (including its diammonium, isopropylammonium and potassium salt), halauxifen-methyl, iodometsulfuron-methyl sodium, MCPA, mesosulfuron-methyl, mesotrione, metribuzin, metsulfuron-methyl, nicosulfuron, S-metolachlor, pinoxaden, prosulfocarb, pyroxsulam and terbuthylazine.
In one embodiment, wherein component B is a compound having the formula B8, preferably R11Is H, C1-C6Alkyl or C1-C6Haloalkyl, more preferably methyl, ethyl or CHF2And still more preferably H or methyl.
Preferably, R6Is H. Preferably Q1Is a phenyl or pyridyl ring, each of which is optionally substituted with 1 to 3R4And (4) substitution. Preferably, Q1Is substituted by 1 to 2R4A substituted phenyl ring. Preferably, Q2Is optionally substituted by 1 at 3R5A substituted phenyl ring. More preferably Q1Is substituted by 1-3R5A substituted phenyl group. Preferably, each R4Independently of each otherIs halogen, C1-C4Alkyl radical, C1-C3Haloalkyl, C1-C3Alkoxy, or C1-C3A haloalkoxy group; more preferably chlorine, fluorine, bromine, C1-C2Haloalkyl, C1-C2Haloalkoxy, or C1-C2An alkoxy group. Preferably, each R5Independently of one another is halogen, C1-C4Alkyl radical, C1-C3Haloalkyl, C1-C3Alkoxy, or C1-C3A haloalkoxy group; more preferably chlorine, fluorine, bromine, C1-C2Haloalkyl, C1-C2Haloalkoxy, or C1-C2An alkoxy group; still more preferably fluorine.
Particularly preferred compounds of formula B8 for use as component B in the compositions of the invention are shown in table B8 below as compounds B801 to B815.
Table B8 compounds having formula (B8) for use in the compositions described herein.
Figure BDA0001826282010000161
Figure BDA0001826282010000171
Figure BDA0001826282010000181
Compounds having formula B8 as described herein may be prepared as described in WO 2015/084796 and WO 2016/094117.
In further embodiments, wherein component B is a compound having the formula B9, it is preferred that p is 1,2, or 3, more preferably 1 or 2. Preferably, n is 1,2 or 3, more preferably 1 or 2. Preferably, R1Is H or C1-C6Alkyl, more preferably H or methyl. In one set of embodiments, R11Is H.
Preferably, each R2Independently of one another are chlorine, fluorine, C1-C3Haloalkyl, or C1-C3Haloalkoxy, more preferably chloro, fluoro, C1Fluoroalkyl (i.e. fluoromethyl, difluoromethyl, trifluoromethyl) C1-fluoroalkoxy (i.e. trifluoromethoxy, difluoromethoxy, fluoromethoxy). Preferably, each R3Independently of one another are chlorine, fluorine, C1-C3Haloalkyl, or C1-C3Haloalkoxy, more preferably chloro, fluoro, C1Fluoroalkyl (i.e. fluoromethyl, difluoromethyl, trifluoromethyl) C1-fluoroalkoxy (i.e. trifluoromethoxy, difluoromethoxy, fluoromethoxy). Particularly preferred compounds of formula B9 for use as component B in the compositions of the invention are shown in table B9 below.
Table B9. compounds having formula B9 (all compounds are in racemic form, unless otherwise specified) for use in the compositions described herein.
Figure BDA0001826282010000191
Figure BDA0001826282010000201
Figure BDA0001826282010000211
Figure BDA0001826282010000221
Figure BDA0001826282010000231
Compounds of formula B9 as described herein may be prepared as described in WO 2016/003997.
In one embodiment, with reference to the compositions mentioned above, component (a) is compound 1.1. In another embodiment, component (a) is compound 1.2, with reference to the compositions mentioned above. In another embodiment, component (a) is compound 1.3 with reference to the compositions mentioned above. In another embodiment, component (a) is compound 1.4 with reference to the compositions mentioned above. In another embodiment, component (a) is compound 1.5, with reference to the compositions mentioned above. In another embodiment, component (a) is compound 1.6, with reference to the compositions mentioned above. In another embodiment, component (a) is compound 1.7 with reference to the compositions mentioned above. In another embodiment, with reference to the compositions mentioned above, component (a) is compound 1.8. In another embodiment, component (a) is compound 1.9 with reference to the compositions mentioned above. In another embodiment, component (a) is compound 1.10, with reference to the compositions mentioned above. In another embodiment, component (a) is compound 1.11 with reference to the compositions mentioned above. In another embodiment, with reference to the compositions mentioned above, component (a) is compound 1.12. In another embodiment, component (a) is compound 1.13 with reference to the compositions mentioned above. In another embodiment, with reference to the compositions mentioned above, component (a) is compound 1.14.
Further example compositions of the invention comprise:
compound 1.1+ acetochlor, compound 1.1+ acifluorfen sodium, compound 1.1+ aclonifen, compound 1.1+ alachlor, compound 1.1+ metolachlor, compound 1.1+ dimethenamid, compound 1.1+ amicarbazone, compound 1.1+ amidosulfuron, compound 1.1+ aminocyclopyrachlor, compound 1.1+ aminopyralid, compound 1.1+ fenflurazon, compound 1.1+ desmetryn, compound 1.1+ asulam, compound 1.1+ atrazine, compound 1.1+ beflubutamid, compound 1.1+ flufenacet, compound 1.1+ bensulfuron methyl, compound 1.1+ bentazone, compound 1.1+ flurtamone, compound 1.1+ aclonifen, compound 1.1+ bispyribac-sodium, compound 1.1+ bufenpyradin, compound 1.1+ bromoxynil, compound 1.1+ butafenacet, compound 1.1+ flufenacetron, compound 1.1+ metolachlor, compound 1.1+ carfentrazone, compound 1+ carfen, Compound 1.1+ cloransularbamic acid, compound 1.1+ chlorimuron ethyl, compound 1.1+ chlortoluron, compound 1.1+ chlorsulfuron, compound 1.1+ cinosulfuron, compound 1.1+ indolone grass ester, compound 1.1+ clethodim, compound 1.1+ clodinafop-propargyl, compound 1.1+ clomazone, compound 1.1+ clopyralid, compound 1.1+ cycloxydim, compound 1.1+ cyhalofop-butyl, compound 1.1+2,4-D (including its choline salt and 2-ethylhexyl ester), compound 1.1+ chlorimuron, compound 1.1+ desmedipham, compound 1.1+ dicamba (including its aluminum, aminopropyl, bisaminopropylmethyl, choline, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salts), compound 1.1+ diclofop-methyl, compound 1.1+ diclosulam, compound 1.1+ diclosularbamate, compound 1.1+ fluazinam, Compound 1.1+ diflufenzopyr, compound 1.1+ dimethenamid, compound 1.1+ diquat dibromide, compound 1.1+ diuron, compound 1.1+ dicamba, compound 1.1+ ethametsulfuron, compound 1.1+ ethofumesate, compound 1.1+ fenoxaprop-ethyl, compound 1.1+ fenquinton, compound 1.1+ fentrazamide, compound 1.1+ flazasulfuron, compound 1.1+ diflufenican, compound 1.1+ fluazifop-butyl, compound 1.1+ fluazifop-sodium, compound 1.1+ flufenacet, compound 1.1+ flumetsulam, compound 1.1+ propyzamide, compound 1.1+ fludaruron-methyl sodium, compound 1.1+ fluroxypyr, compound 1+ flufenacet-methyl, compound 1.1+ flufenacet-1.1.1 + flufenacet, compound 1.1+ flufenacet-methyl ester, compound 1, Compound 1.1+ foramsulfuron, compound 1.1+ glufosinate (including ammonium salt thereof), compound 1.1+ glyphosate (including diammonium salt, isopropylammonium salt and potassium salt thereof), compound 1.1+ halauxifen-ethyl, compound 1.1+ halosulfuron-methyl, compound 1.1+ haloxyfop-methyl, compound 1.1+ hexazinone, compound 1.1+ imazamethabenz-ethyl, compound 1.1+ imazethapyr-methyl, compound 1.1+ imazapyr, compound 1.1+ imazaquin, compound 1.1+ imazethapyr, compound 1.1+ indamine, compound 1.1+ iodometsulfuron-methyl sodium, compound 1.1+ iodosulfuron-methyl sodium, compound 1.1+ iodobenzonitrile, compound 1.1+ triafamone, compound 1.1+ isoproturon, compound 1.1+ isoxaflutolon-methyl, compound 1.1+ flutolanil-methyl, compound 1.1+ flutolmeturon-methyl, Compound 1.1+ MCPA, compound 1.1+ chloropropionic acid, compound 1.1+ mefenacet, compound 1.1+ methyldisulfuron-methyl, compound 1.1+ mesotrione, compound 1.1+ metamitron, compound 1.1+ metazachlor, compound 1.1+ taruron, compound 1.1+ metolachlor, compound 1.1+ metoxuron, compound 1.1+ cyclizine, compound 1.1+ metsulfuron-methyl, compound 1.1+ molydate, compound 1.1+ dichlor, compound 1.1+ nicosulfuron, compound 1.1+ daloxaden, compound 1.1+ oxadiazon, compound 1.1+ oxadiargyl, compound 1.1+ epoxysulfuron, compound 1.1+ oxaziclomefone, compound 1.1+ oxyfluorfen, compound 1.1+ ethoxyfen-ethyl, compound 1.1+ dichlor, compound 1.1+ penoxsulam Compound 1.1+ dimethenamid, compound 1.1+ betanin, compound 1.1+ picloram, compound 1.1+ flupyraflufen, compound 1.1+ pinoxaden, compound 1.1+ pretilachlor, compound 1.1+ primisulfuron methyl, compound 1.1+ prodiamine, compound 1.1+ prometryn, compound 1.1+ propyzamide, compound 1.1+ propanil, compound 1.1+ propaquizafop, compound 1.1+ propbensulfuron, compound 1.1+ propyzate, compound 1.1+ prosulfocarb, compound 1.1+ pyrazosulfuron ethyl, compound 1.1+ pyribenzoxim, compound 1.1+ pyridate, compound 1.1+ pyriftalid, compound 1.1+ pyriminobac-methyl, compound 1.1+ metosulam, Compound 1.1+ quizalofop-p-ethyl, compound 1.1+ rimsulfuron, compound 1.1+ saflufenacil, compound 1.1+ sethoxydim, compound 1.1+ S-metolachlor, compound 1.1+ sulcotrione, compound 1.1+ sulfentrazone, compound 1.1+ sulfometyl methyl, compound 1.1+ sulfometuron, compound 1.1+ buthiuron, compound 1.1+ tefurotrizone, compound 1.1+ tembotrione, compound 1.1+ terbuthylazine, compound 1.1+ desmetryn, compound 1.1+ thiencarbazone, compound 1.1+ thifensulfuron, compound 1.1+ tiafenacil, compound 1.1+ topride, compound 1.1+ topramezone, compound 1.1+ metribuzin, compound 1.1+ flutolmeturon, compound 1.1+ triallate, compound 1.1+ triasulfuron, compound 1.1+ metosultap-methyl, compound 1.1+ trifloxysulfuron, compound 1.1.1 + metosultap-methyl, compound 1.1 Compound 1.1+ trifluralizin, compound 1.1+ trifluralin, compound 1.1+ triflusulfuron-methyl, and compound 1.1+ 4-amino-3-chloro-6- (4-chloro-2-fluoro-3-methoxyphenyl) -5-fluoropyridine-2-carboxylate; (Compound B1), 1.1+ 4-hydroxy-1-methoxy-5-methyl-3- [4- (trifluoromethyl) -2-pyridinyl ] imidazolidin-2-one (Compound B2), 1.1+ 4-hydroxy-1, 5-dimethyl-3- [4- (trifluoromethyl) -2-pyridinyl ] imidazolidin-2-one (Compound B3), 1.1+ 5-ethoxy-4-hydroxy-1-methyl-3- [4- (trifluoromethyl) -2-pyridinyl ] imidazolidin-2-one (Compound B4), 1.1+ 4-hydroxy-1-methyl-3- [4- (trifluoromethyl) -2-pyridinyl ] imidazolidin-2-one (Compound B5), 1.1+ 4-hydroxy-1, 5-dimethyl-3- [ 1-methyl-5- (trifluoromethyl) pyrazol-3-yl ] imidazolidin-2-one (compound B6), 1.1+ (4R)1- (5-tert-butylisoxazol-3-yl) -4-ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one (compound B7);
compound 1.1+ N- (2-fluorophenyl) -2-oxo-4- [3- (trifluoromethyl) phenyl ] -pyrrolidine-3-carboxamide (Compound B801), Compound 1.1+ N- (2, 3-difluorophenyl) -2-oxo-4- [3- (trifluoromethyl) phenyl ] pyrrolidine-3-carboxamide (Compound B802), Compound 1.1+ 2-oxo-4- [3- (trifluoromethyl) phenyl ] -N- (2,3, 4-trifluorophenyl) pyrrolidine-3-carboxamide (Compound B803), Compound 1.1+ N- (2-fluorophenyl) -1-methyl-2-oxo-4- [3- (trifluoromethyl) phenyl ] pyrrolidine-3-carboxamide (Compound B801) B804) The compound 1.1+ N- (2-fluorophenyl) -2-oxo-4- [4- (trifluoromethyl) phenyl ] pyrrolidine-3-carboxamide (compound B805), the compound 1.1+ N- (2-fluorophenyl) -1-methyl-2-oxo-4- [4- (trifluoromethyl) phenyl ] pyrrolidine-3-carboxamide (compound B806), the compound 1.1+ N- (2, 3-difluorophenyl) -2-oxo-4- [4- (trifluoromethyl) phenyl ] pyrrolidine-3-carboxamide (compound B807), the compound 1.1+ N- (2, 3-difluorophenyl) -1-methyl-2-oxo-4- [4- (trifluoromethyl) phenyl ] pyrrolidine-3- Carboxamide (Compound B808), Compound 1.1+ 2-oxo-4- [4- (trifluoromethyl) phenyl ] -N- (2,3, 4-trifluorophenyl) pyrrolidine-3-carboxamide (Compound B809), Compound 1.1+ N- (2-fluorophenyl) -4- (4-fluorophenyl) -1-methyl-2-oxo-pyrrolidine-3-carboxamide (Compound B810), Compound 1.1+ N- (2, 3-difluorophenyl) -4- (3, 4-difluorophenyl) -2-oxo-pyrrolidine-3-carboxamide (Compound B811), Compound 1.1+4- (3, 4-difluorophenyl) -N- (2-fluorophenyl) -2-oxo-pyrrolidine-3- Carboxamide (compound B812), compound 1.1+ N- (2, 4-difluorophenyl) -4- (3, 5-difluorophenyl) -2-oxo-pyrrolidine-3-carboxamide (compound B813), compound 1.1+ N- (2, 3-difluorophenyl) -4- (3-isopropylphenyl) -2-oxo-pyrrolidine-3-carboxamide (compound B814), compound 1.1+ N- (2, 3-difluorophenyl) -2-oxo-4- [6- (trifluoromethyl) -3-pyridinyl ] pyrrolidine-3-carboxamide (compound B815);
compound 1.1+4- (3, 4-difluorophenyl) -2-oxo-N- [2- (trifluoromethyl) phenyl ] -piperidine-3-carboxamide (Compound B901), Compound 1.1+ N- (2, 3-difluorophenyl) -2-oxo-4- [3- (trifluoromethyl) phenyl ] piperidine-3-carboxamide (Compound B902), Compound 1.1+ 2-oxo-N- [2- (trifluoromethyl) phenyl ] -4- [3- (trifluoromethyl) phenyl ] piperidine-3-carboxamide (Compound B903), Compound 1.1+ N- (2-chlorophenyl) -2-oxo-4- [4- (trifluoromethyl) phenyl ] piperidine-3-carboxamide (Compound B904), The compound 1.1+ N- (2-fluorophenyl) -2-oxo-4- [4- (trifluoromethyl) phenyl ] piperidine-3-carboxamide (compound B905), the compound 1.1+ (3R,4S) -N- (2, 3-difluorophenyl) -2-oxo-4- [3- (trifluoromethyl) phenyl ] piperidine-3-carboxamide (compound B906), the compound 1.1+ (3R,4S) -N- (2, 3-difluorophenyl) -2-oxo-4- [4- (trifluoromethyl) phenyl ] piperidine-3-carboxamide (compound B907), the compound 1.1+ (3R,4S) -N- (3-chloro-2-fluoro-phenyl) -2-oxo-4- [3- (tris- Fluoromethyl) phenyl ] piperidine-3-carboxamide (Compound B908), the Compound 1.1+ (3R,4S) -2-oxo-4- [3- (trifluoromethyl) phenyl ] -N- (2,3, 4-trifluorophenyl) piperidine-3-carboxamide (Compound 909), the Compound 1.1+ N- (2, 3-difluorophenyl) -2-oxo-4-phenyl-piperidine-3-carboxamide (Compound B910), the Compound 1.1+ N- (2-fluorophenyl) -2-oxo-4- [3- (trifluoromethoxy) phenyl ] piperidine-3-carboxamide (Compound B911), the Compound 1.1+ 2-oxo-4- [3- (trifluoromethoxy) phenyl ] -N- [2- (trifluoromethyl) benzene Phenyl ] piperidine-3-carboxamide (compound B912), the compound 1.1+ N- (2, 3-difluorophenyl) -2-oxo-4- [3- (trifluoromethoxy) phenyl ] piperidine-3-carboxamide (compound B913), the compound 1.1+ (3R,4S) -4- (3-chlorophenyl) -N- (2, 3-difluorophenyl) -2-oxo-piperidine-3-carboxamide (compound B914), the compound 1.1+4- [3- (difluoromethyl) phenyl ] -2-oxo-N- (2,3, 4-trifluorophenyl) piperidine-3-carboxamide (compound B915), the compound 1.1+4- [3- (difluoromethyl) phenyl ] -N- (2-fluorophenyl) -2-oxo 3-oxo-piperidine-carboxamide (compound B916), compound 1.1+4- [3- (difluoromethyl) phenyl ] -N- (2, 3-difluorophenyl) -2-oxo-piperidine-3-carboxamide (compound B917), compound 1.1+ (3R,4S) -N- (2, 3-difluorophenyl) -4- (4-fluorophenyl) -2-oxo-piperidine-3-carboxamide (compound B918), and compound 1.1+ (3R,4S) -4- (4-fluorophenyl) -2-oxo-N- [2- (trifluoromethyl) phenyl ] piperidine-3-carboxamide (compound B919).
In another embodiment, component compound 1.1 is replaced with compound 1.2 with reference to the compositions mentioned above. In another embodiment, component compound 1.1 is replaced with compound 1.3 with reference to the compositions mentioned above. In another embodiment, component compound 1.1 is replaced with compound 1.4 with reference to the compositions mentioned above. In another embodiment, component compound 1.1 is replaced with compound 1.5 with reference to the compositions mentioned above. In another embodiment, component compound 1.1 is replaced with compound 1.6 with reference to the compositions mentioned above. In another embodiment, component compound 1.1 is replaced with compound 1.7 with reference to the compositions mentioned above. In another embodiment, component compound 1.1 is replaced with compound 1.8 with reference to the compositions mentioned above. In another embodiment, component compound 1.1 is replaced with compound 1.9 with reference to the compositions mentioned above. In another embodiment, component compound 1.1 is replaced with compound 1.10 with reference to the compositions mentioned above. In another embodiment, component compound 1.1 is replaced with compound 1.11 with reference to the compositions mentioned above. In another embodiment, component compound 1.1 is replaced with compound 1.12 with reference to the compositions mentioned above. In another embodiment, component compound 1.1 is replaced with compound 1.13 with reference to the compositions mentioned above. In another embodiment, component compound 1.1 is replaced with compound 1.14 with reference to the compositions mentioned above.
The mixing ratio of the compound of the formula (I) to the mixed partner B may vary depending on the nature of the mixed partner or partners. Typical ratios include, for example, from 1:100 to 1000:1, from 1:50 to 50:1, or from 1:10 to 10: 1.
Although binary mixtures of the compound of formula (I) with another herbicide are specifically disclosed above, one of ordinary skill in the art will appreciate that the invention extends to ternary, as well as additional combinations comprising the above binary mixtures. In particular, the present invention provides compositions comprising the ternary mixtures listed in table 1 below (CMP ═ compounds: see table C1):
TABLE 1
Figure BDA0001826282010000291
Figure BDA0001826282010000301
Figure BDA0001826282010000311
Figure BDA0001826282010000321
Figure BDA0001826282010000331
Figure BDA0001826282010000341
Figure BDA0001826282010000351
Figure BDA0001826282010000361
Figure BDA0001826282010000371
The present invention further provides compositions as defined in tables 2 to 14 below.
Table 2. compositions comprising the ternary mixtures listed in table 1 above, wherein compound 1.1 is replaced by compound 1.2 (see table C1).
Table 3. compositions comprising the ternary mixtures listed in table 1 above, wherein compound 1.1 is replaced by compound 1.3 (see table C1).
Table 4. compositions comprising the ternary mixtures listed in table 1 above, wherein compound 1.1 is replaced by compound 1.4 (see table C1).
Table 5. compounds comprising the ternary mixtures listed in table 1 above, wherein compound 1.1 is replaced by compound 1.5 (see table C1).
Table 6. compounds comprising the ternary mixtures listed in table 1 above, wherein compound 1.1 is replaced by compound 1.6 (see table C1).
Table 7. compounds comprising the ternary mixtures listed in table 1 above, wherein compound 1.1 is replaced by compound 1.7 (see table C1).
Table 8. compounds comprising the ternary mixtures listed in table 1 above, wherein compound 1.1 is replaced by compound 1.8 (see table C1).
Table 9. compounds comprising the ternary mixtures listed in table 1 above, wherein compound 1.1 is replaced by compound 1.9 (see table C1).
Table 10. compounds comprising the ternary mixtures listed in table 1 above, wherein compound 1.1 is replaced by compound 1.10 (see table C1).
Table 11. compounds comprising the ternary mixtures listed in table 1 above, wherein compound 1.1 is replaced by compound 1.11 (see table C1).
Table 12. compounds comprising the ternary mixtures listed in table 1 above, wherein compound 1.1 is replaced by compound 1.12 (see table C1).
Table 13. compounds comprising the ternary mixtures listed in table 1 above, wherein compound 1.1 is replaced by compound 1.13 (see table C1).
Table 14. compounds comprising the ternary mixtures listed in table 1 above, wherein compound 1.1 is replaced by compound 1.14 (see table C1).
The compositions of the present invention may further comprise one or more safeners. In particular, the following safeners are particularly preferred: AD 67(MON 4660), benoxacor, cloquintocet-mexyl, oxabetrinil, cyprosulfamide, dichlormid, dicyclonon, diethanolate (diethholate), fenchlorazole, fenclorim, fenchlorazole, fluxofenapyr, furazone, isoxadifen, mefenpyr, mefenacet, mefenamate, oxabetrinil, naphthalic anhydride (CAS RN 81-84-5), TI-35, N-isopropyl-4- (2-methoxy-benzoylsulfamoyl) -benzamide (CAS RN 221668-34-4) and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide. Preferably, the mixing ratio of the compound of the formula I to the safener is from 100:1 to 1:10, in particular from 20:1 to 1: 1.
Particularly preferred safeners are cloquintocet-mexyl, cyprosulfamide, isoxadifen, mefenpyr-diethyl and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Preferred compositions and safeners of the invention include:
compound 1.1, atrazine and cloquintocet; compound 1.1, atrazine and cyprosulfamide; compound 1.1, atrazine and isoxadifen; compound 1.1, atrazine and mefenpyr-diethyl; compound 1.1, atrazine and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, terbuthylazine and cloquintocet; compound 1.1, terbuthylazine and cyclopropanesulfonamide; compound 1.1, terbuthylazine and isoxadifen; compound 1.1, terbuthylazine and mefenpyr-diethyl; compound 1.1, terbuthylazine and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, mesotrione and cloquintocet; compound 1.1, mesotrione and cyprosulfamide; compound 1.1, mesotrione and isoxadifen; compound 1.1, mesotrione and mefenpyr-diethyl; compound 1.1, mesotrione and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, bicyclic pyrone and detoxiquinoline; compound 1.1, bicyclic pyrones and cyclopropanesulfonamide; compound 1.1, bicyclic pyrone and bisbenzoxazole acid; compound 1.1, bicyclic pyrone and mefenpyr-diethyl; compound 1.1, bicyclic pyrone and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, nicosulfuron, and cloquintocet-mexyl; compound 1.1, nicosulfuron, and cyprosulfamide; 1.1 of a compound, nicosulfuron and isoxadifen; compound 1.1, nicosulfuron and mefenpyr-diethyl; compound 1.1, nicosulfuron, and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, S-metolachlor and cloquintocet-mexyl; compound 1.1, S-metolachlor and cyprosulfamide; compound 1.1, S-metolachlor and isoxadifen; compound 1.1, S-metolachlor and mefenpyr-diethyl; the compounds 1.1, S-metolachlor and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, bromoxynil and cloquintocet-mexyl, compound 1.1, bromoxynil and cyclopropanesulfonamide, compound 1.1, bromoxynil and isoxadifen-ethyl, compound 1.1, bromoxynil and mefenpyr-diethyl, compound 1.1, bromoxynil and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, pinoxaden and cloquintocet-mexyl, compound 1.1, pinoxaden and cyprosulfamide, compound 1.1, pinoxaden and isoxadifen, compound 1.1, pinoxaden and mefenpyr-diethyl, compound 1.1, pinoxaden and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, clodinafop-propargyl and cloquintocet-mexyl, compound 1.1, clodinafop-propargyl and cyclopropylsulfonamide, compound 1.1, clodinafop-propargyl and isoxadifen-yl, compound 1.1, clodinafop-propargyl and mefenpyr-diethyl, compound 1.1, clodinafop-propargyl and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, fenoxaprop-ethyl and cloquintocet-mexyl, compound 1.1, fenoxaprop-ethyl and cyprosulfamide, compound 1.1, fenoxaprop-ethyl and isoxadifen-ethyl, compound 1.1, fenoxaprop-ethyl and mefenpyr-diethyl, compound 1.1, fenoxaprop-ethyl and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, mesosulfuron and cloquintocet-mexyl, compound 1.1, mesosulfuron and cyprosulfamide, compound 1.1, mesosulfuron and isoxadifen-yl, compound 1.1, mesosulfuron and mefenpyr-diethyl, compound 1.1, mesosulfuron and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, iodosulfuron methyl sodium and cloquintocet-mexyl, compound 1.1, iodosulfuron methyl sodium and cyprosulfamide, compound 1.1, iodosulfuron methyl sodium and isoxadifen-ethyl, compound 1.1, iodosulfuron methyl sodium and mefenpyr-diethyl, compound 1.1, iodosulfuron methyl sodium and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, thiencarbazone-methyl and cloquintocet-mexyl, compound 1.1, thiencarbazone-methyl and cyprosulfamide, compound 1.1, thiencarbazone-methyl and isoxadifen-ethyl, compound 1.1, thiencarbazone-methyl and mefenpyr-diethyl, compound 1.1, thiencarbazone-methyl and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, compound B2 and detoxified quinoline, compound 1.1, compound B2 and cyclopropanesulfonamide, compound 1.1, compound B2 and bisbenzoxazole acid, compound 1.1, compound B2 and mefenpyr-diethyl, compound 1.1, compound B2 and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, compound B3 and detoxified quinoline, compound 1.1, compound B3 and cyclopropanesulfonamide, compound 1.1, compound B3 and bisbenzoxazole acid, compound 1.1, compound B3 and mefenpyr-diethyl, compound 1.1, compound B3 and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, compound B4 and detoxified quinoline, compound 1.1, compound B4 and cyclopropanesulfonamide, compound 1.1, compound B2 and bisbenzoxazole acid, compound 1.1, compound B4 and mefenpyr-diethyl, compound 1.1, compound B4 and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, compound B5 and detoxified quinoline, compound 1.1, compound B5 and cyclopropanesulfonamide, compound 1.1, compound B5 and bisbenzoxazole acid, compound 1.1, compound B5 and mefenpyr-diethyl, compound 1.1, compound B5 and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, compound B6 and detoxified quinoline, compound 1.1, compound B6 and cyclopropanesulfonamide, compound 1.1, compound B6 and bisbenzoxazole acid, compound 1.1, compound B6 and mefenpyr-diethyl, compound 1.1, compound B6 and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Compound 1.1, compound B7 and detoxified quinoline, compound 1.1, compound B7 and cyclopropanesulfonamide, compound 1.1, compound B7 and bisbenzoxazole acid, compound 1.1, compound B7 and mefenpyr-diethyl, compound 1.1, compound B7 and N- (2-methoxybenzoyl) -4- [ (methylaminocarbonyl) amino ] benzenesulfonamide.
Further preferred compositions and safeners of the invention include those defined above in which compound 1.1 is substituted by compound 1.2. Further preferred compositions and safeners of the invention include those defined above in which compound 1.1 is substituted by compound 1.3. Further preferred compositions and safeners of the invention include those defined above in which compound 1.1 is substituted by compound 1.4. Further preferred compositions and safeners of the invention include those defined above in which compound 1.1 is substituted by compound 1.5. Further preferred compositions and safeners of the invention include those defined above in which compound 1.1 is substituted by compound 1.6. Further preferred compositions and safeners of the invention include those defined above in which compound 1.1 is substituted by compound 1.7. Further preferred compositions and safeners of the invention include those defined above in which compound 1.1 is substituted by compound 1.8. Further preferred compositions and safeners of the invention include those defined above in which compound 1.1 is substituted by compound 1.9. Further preferred compositions and safeners of the invention include those defined above in which compound 1.1 is substituted by compound 1.10. Further preferred compositions and safeners of the invention include those defined above in which compound 1.1 is substituted by compound 1.11. Further preferred compositions and safeners of the invention include those defined above in which compound 1.1 is substituted by compound 1.12. Further preferred compositions and safeners of the invention include those defined above in which compound 1.1 is substituted by compound 1.13. Further preferred compositions and safeners of the invention include those defined above in which compound 1.1 is substituted by compound 1.14.
The compounds of formula I can also be used in mixtures with other agrochemicals, such as fungicides, nematicides or insecticides, examples of which are given in The Pesticide Manual, sixteenth edition, The british crop protection council, 2012.
The present invention still further provides a method of controlling weeds at a locus, said method comprising applying to the locus a weed controlling amount of a composition comprising a compound having formula (I). Furthermore, the present invention further provides a method of selectively controlling weeds at a locus comprising crop plants and weeds, wherein the method comprises applying to the locus a weed controlling amount of a composition according to the invention. By 'controlling' is meant killing, reducing or delaying growth or preventing or reducing germination. The plants to be controlled are usually unwanted plants (weeds). By 'locus' is meant the area where plants are growing or will grow. The application may be to the locus pre-and/or post-emergence of the crop plants. Some crop plants may be inherently tolerant to the herbicidal effects of compounds having formula (I). Preferred crop plants include corn, wheat, barley and rice. However, in some cases, it may be desirable to design tolerance into crop plants, for example by genetic engineering. It is therefore possible that the crop plants are genetically engineered to confer tolerance to 4-hydroxyphenylpyruvate dioxygenase (HPPD) -inhibitors. Methods of conferring tolerance to HPPD-inhibitors to crop plants are known, for example, from WO 0246387. Thus, in an even more preferred embodiment, the crop plant is transgenic for a polynucleotide comprising a DNA sequence encoding an HPPD inhibitor-resistant HPPD enzyme derived from a bacterium, more particularly from Pseudomonas fluorescens (Pseudomonas fluorescens) or Shewanella colwelliana (Shewanella colwelliana), or from a plant, more particularly from a monocot or still more particularly from a barley, maize, wheat, rice, brachypodium, tribulus (Cenchrus), lolium, fescue, setaria, crickets, sorghum or avena species. Several HPPD-tolerant soybean transgene "events" are known and include, for example, SYHT04R (WO 2012/082542), SYHT0H2(WO 2012/082548), and FG 72. Accordingly, the herbicidal compounds of the present invention have been widely applied to many crop plants, including cereals, such as barley and wheat, cotton, oilseed rape, sunflower, corn, rice, soybean, sugar beet, sugar cane and turf. Crop plants may also include trees, such as fruit trees, palm trees, coconut trees, or other nuts. Also included are vines (such as grapes), shrub trees, fruit plants and vegetables.
The application rate of the compounds of formula I can vary within wide limits and depends on the nature of the soil, the method of application (pre-or post-emergence; seed dressing; application to seed furrows; no-tillage application, etc.), the crop plants, the weeds to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application, and the target crop. The compounds of formula I according to the invention are generally applied at a rate of from 10 to 2000g/ha, especially from 25 to 1000g/ha, more especially from 25 to 250 g/ha.
Application is usually by spraying the composition, typically by tractor mounted spray machines for large areas, but other methods such as dusting (for powders), dripping or drenching may also be used.
Crop plants are to be understood as also including those which have been rendered tolerant to other herbicides or classes of herbicides (for example ALS-inhibitors, GS-inhibitors, EPSPS-inhibitors, PPO-inhibitors, and accase-inhibitors) by conventional breeding methods or by genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones (e.g., imazethapyr) by conventional breeding methods is
Figure BDA0001826282010000441
Summer rape (canola). Examples of crops which have been rendered tolerant to herbicides by genetic engineering include, for example, glyphosate-and glufosinate-resistant corn varieties, among others
Figure BDA0001826282010000442
And
Figure BDA0001826282010000443
commercially available under the trade name.
Crop plants are also to be understood as being those crop plants which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to european corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to colorado beetle). Examples of Bt corn are
Figure BDA0001826282010000444
Bt 176 maize hybrid (Syngenta Seeds, Inc.). Bt toxins are proteins naturally formed by bacillus thuringiensis soil bacteria. Examples of toxins or transgenic plants capable of synthesizing such toxins are described in EP-A-451878, EP-A374753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427529. Examples of transgenic plants comprising one or more genes encoding insecticide resistance and expressing one or more toxins are
Figure BDA0001826282010000445
(corn),
Figure BDA0001826282010000446
(corn),
Figure BDA0001826282010000447
(cotton),
Figure BDA0001826282010000448
(cotton),
Figure BDA0001826282010000449
(potato),
Figure BDA00018262820100004410
And
Figure BDA00018262820100004411
both the plant crop and seed material can be resistant to herbicides and at the same time resistant to insect feeding ("stacked" transgenic events). For example, the seed may be glyphosate tolerant while having the ability to express an insecticidal Cry3 protein.
Crop plants are also to be understood as including those which are obtained by conventional breeding or genetic engineering methods and comprise so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).
These compositions can be used to control unwanted vegetation (collectively referred to as 'weeds'). The weeds to be controlled can be both monocotyledonous species, such as agrostis, alopecurus, avena, brachiaria, bromus, tribulus, cyperus, digitaria, barnyard grass, eleusine, lolium, monochoria, cymbopogon, sagittaria, arrowhead, scripus, setaria and sorghum, and dicotyledonous species, such as abutilon, amaranthus, ragweed, chenopodium, chrysanthemum, oenothera, ratula, ipomoea, eclipta, sida, sinapis, solanum, chickweed, veronica, viola and xanthium.
In a further aspect of the invention there is provided the use of a compound of formula (I) as defined herein as a herbicide.
These compounds of the invention can be prepared according to the following schemes.
The preparation of the compounds of formula (I) is carried out analogously to known methods and comprises reacting a compound of formula (IIc):
Figure BDA0001826282010000451
wherein R is1Is as defined for formula (I), and LG is a suitable leaving group, e.g. a halogen atom, such as chlorine, or an alkoxy or aryloxy group, such as 4-nitrophenoxy, reacted with a diketone of formula (III) in an inert organic solvent, e.g. dichloromethane or acetonitrile, in the presence of a base such as triethylamine
Figure BDA0001826282010000452
Wherein
A1And Ra、Rb、Rc、RdIs as defined above for formula (I);
to give an ester of formula (IV):
Figure BDA0001826282010000461
a catalyst such as 4-dimethylaminopyridine or acetone cyanohydrin, or a metal cyanide salt such as sodium cyanide, may be used to rearrange in the presence of a suitable base such as triethylamine to give a compound of formula (I).
Thus, according to a further aspect of the present invention there is provided a compound having formula (II)
Figure BDA0001826282010000462
Wherein
R1Is as defined above, and R2Selected from the group consisting of: halogen, -OH, C1-C6Alkoxy, aryloxy, and N-linked imidazolyl. In this context, aryloxy is preferably a phenoxy group optionally substituted on the phenyl ring by 1 to 5 groups consisting of: fluorine, chlorine, nitro, cyano, C1-C3Alkyl radical, C1-C3Alkoxy and C1-C3A haloalkyl group. Thus, specific examples of the preferred aryloxy group include phenoxy group, 4-nitrophenoxy group and 2,3,4,5, 6-pentafluorophenoxy group.
Table C2-examples of compounds of the invention.
Figure BDA0001826282010000471
Figure BDA0001826282010000472
Figure BDA0001826282010000481
The diketones of formula (III) can be commercially available or, where not, can be prepared by methods detailed in the literature. For example, preparation of diketones (wherein A1Is C ═ O and Ra、Rb、RcAnd RdAll methyl) are described in detail in Tetrahedron]2013,8559 and 8563. Preparation of diketones (wherein A1Is CH (ethyl) and Ra、Rb、RcAnd RdAll are hydrogen) are described in detail in Tetrahedron]2000,4753 and 4758.Preparation of diketones (wherein A1Is CH2，Ra-Rcis-CH2CH2-and RbAnd RdAll hydrogen) are described in detail in Tetrahedron Lett [ Tetrahedron communication]2013, 557-. Preparation of diketones (wherein A1Is CH2And R isa、Rb、RcAnd RdBoth methyl) are described in detail in US 5006150A1, 1991.
Thus, according to a further aspect of the present invention there is provided a process for the production of a compound of formula (I), said process comprising (I) reacting a compound of formula (IIc):
Figure BDA0001826282010000491
wherein R is1Is as defined for formula (I) and LG is a suitable leaving group (e.g. a halogen atom, such as chlorine, or an alkoxy or aryloxy group, such as 4-nitrophenoxy) with a diketone of formula (III)
Figure BDA0001826282010000492
And (ii) rearranging the resulting product into a compound having formula (I).
The compound having formula (IIc) may be prepared from a carboxylic acid having formula (IIb).
Figure BDA0001826282010000493
For example, for LG ═ chloride, the skilled person will recognize the usual method to perform this conversion, e.g. treating the carboxylic acid with 1 equivalent of oxalyl chloride and catalytic amounts of N, N-dimethylformamide in a non-polar solvent (e.g. dichloromethane or acetonitrile).
Figure BDA0001826282010000494
The carboxylic acids of formula (IIb) can in turn be prepared from esters of formula (IIa) by treatment with an alkoxide base, such as lithium hydroxide, in a suitable solvent system of a mixture of water and an organic solvent. Examples of suitable esters are those wherein R is2Is C1-C6Alkyl-, such as methyl, ethyl, n-propyl and isopropyl. Examples of suitable solvent systems are tetrahydrofuran/water (1:1) or ethanol/water (1: 1).
Figure BDA0001826282010000501
The ester of formula (IIa) can be prepared from the Chan-Lam coupling between the pyridazinone of formula (IV) and 3, 4-dimethoxyboronic acid. The Chan-Lam reaction is described in detail in Tetrahedron Lett. [ Tetrahedron communication ]1998, 2933-. These reactions use copper (II) or a copper (I) salt such as copper (II) acetate, a non-polar solvent such as dichloromethane or 1, 2-dichloroethane and an organic base such as triethylamine or pyridine or a 1:1 mixture of triethylamine and pyridine. Superstoichiometric equivalents of copper (I) or copper (II) salt may be used, typically 1-3 equivalents of copper (II) acetate. Alternatively, if >1 equivalent of oxidizing agent is also added, a catalytic amount of copper catalyst may be used, for example 0.05 to 0.3 molar equivalents of copper (II) acetate. Suitable examples of oxidizing agents are pyridine-N-oxide or air or oxygen bubbled through the reaction mixture. The reaction can generally be carried out at room temperature to achieve an acceptable conversion in 2-16 h.
Figure BDA0001826282010000502
The pyridazinone having the formula (IV) can be prepared by oxidizing the dihydropyridazinones having the formula (VI) with a suitable oxidizing agent. Examples of suitable oxidizing agents are bromine in solution in acetic acid or dichloromethane, or iodobenzene diacetate in solution in isopropanol.
Figure BDA0001826282010000511
The dihydropyridazinones of formula (VI) can be prepared by treating the compounds of formula (VII) with hydrazine hydrate in a suitable solvent such as ethanol under reflux conditions.
Figure BDA0001826282010000512
The compound having formula (VII) may be prepared by alkylation of a commercially available dialkyl malonate, for example diethyl malonate, with a bromoketone having formula (VIII) in the presence of a suitable base, for example potassium carbonate, in a suitable solvent, for example acetone.
Figure BDA0001826282010000513
The compounds of formula (VIII) may be commercially available or alternatively they may be prepared by treating a commercially available methyl ketone of formula (IX) with bromine in a suitable solvent such as methanol or a mixture of water and glacial acetic acid (about 5: 1).
The following non-limiting examples provide specific synthetic methods for representative compounds useful in the present invention, as shown in table C1 above.
Preparation example 1: preparation of 6- [ 6-cyclopropyl-2- (3, 4-dimethoxyphenyl) -3-oxo-pyridazine-4-carbonyl ] -2,2,4, 4-tetramethyl-cyclohexane-1, 3, 5-trione (compound 1.11 (see Table C1)).
Step 1.2-bromo-1-cyclopropyl-ethanone preparation.
Figure BDA0001826282010000514
To a stirred solution of 1-cyclopropylethanone (50g, 595mmol) in MeOH (350mL) (ice bath) was added bromine (32mL, 595mmol) dropwise over a period of 1 hour at 0 ℃ (the initial red color of the reaction mixture became colorless at the end of the bromine addition). The resulting solution was then stirred at less than 5 ℃ for 4 hours and then addedWater (175mL) was added and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was poured into water (1000mL) and CH was used2Cl2(2X 1000 mL). The combined organic layers were washed with saturated NaHCO3Aqueous solution (500mL), water (500mL) and finally washed with brine (500 mL). Subjecting the organic layer to Na2SO4Dried, filtered and concentrated in vacuo to give a light brown oil. Pure 2-bromo-1-cyclopropyl-ethanone (59g, 61%) was obtained by vacuum distillation of the crude oil at 100 ℃.
1H NMR(400MHz,CDCl3)δ＝4.01(s,2H),2.22-2.17(m,1H),1.14-1.11(m,2H),1.03-0.99(m,2H)。
Step 2. preparation of diethyl 2- (2-cyclopropyl-2-oxo-ethyl) malonate.
Figure BDA0001826282010000521
To a stirred solution of 2-bromo-1-cyclopropyl-ethanone (50g, 307mmol) in acetone (450mL) at room temperature was added K2CO3(64g, 460mmol), potassium iodide (1.5g, 9.2mmol) and diethyl malonate (54g, 337mmol) and the resulting mixture was heated at reflux (75 ℃ C.) for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated in vacuo. The crude material was purified by column chromatography, eluting with 8% EtOAc in hexanes to give diethyl 2- (2-cyclopropyl-2-oxo-ethyl) malonate (40g, 54%) as a light yellow oil.
1H NMR(400MHz,CDCl3)δ＝4.24-4.13(m,4H),3.95(t,1H),3.18(d,2H),1.98-1.92(m,1H),1.26(t,6H),1.06-1.03(m,2H),0.93-0.88(m,2H)。
Step 3. preparation of ethyl 3-cyclopropyl-6-oxo-4, 5-dihydro-1H-pyridazine-5-carboxylate.
Figure BDA0001826282010000531
To a stirred solution of diethyl 2- (2-cyclopropyl-2-oxo-ethyl) malonate (70g, 289mmol) in EtOH (500mL) was added hydrazine hydrate (16mL, 318mmol) dropwise at between 0 ℃ to 5 ℃ in an ice-water bath and the resulting solution was stirred at room temperature for 20 hours. All volatiles were removed from the reaction mixture in vacuo to give crude ethyl 3-cyclopropyl-6-oxo-4, 5-dihydro-1H-pyridazine-5-carboxylate (52g, crude) as a thick yellow oil. The crude material was used in the next step without any further purification.
Step 4. preparation of ethyl 3-cyclopropyl-6-oxo-1H-pyridazine-5-carboxylate.
Figure BDA0001826282010000532
To a stirred solution of ethyl 3-cyclopropyl-6-oxo-4, 5-dihydro-1H-pyridazine-5-carboxylate (52g crude, 247mmol) in AcOH (500mL) was added dropwise a solution of bromine (20mL, 317mmol) in AcOH (200mL) over a period of 30 minutes at between 10 ℃ and 15 ℃. The resulting solution was then stirred at room temperature for an additional 30 minutes. AcOH was removed from the reaction mixture in vacuo. To the residue were added EtOAc (2000mL) and water (5000mL) and the mixture was shaken well. All insoluble particles were then removed by filtration through a celite bed, and the filtrate layer was then separated. The aqueous layer was further extracted with EtOAc (1000 mL). The combined EtOAc layers were washed with saturated NaHCO3Aqueous solution (500mL), saturated Na2S2O3Aqueous solution (500mL) and final brine (500 mL). Subjecting the organic layer to Na2SO4Dried, filtered and concentrated in vacuo. The crude material was purified by column chromatography, eluting with 8% EtOAc in hexanes to give the desired product as a light yellow solid. The solid was further purified by trituration with a 1% solution of EtOAc in hexanes to give ethyl 3-cyclopropyl-6-oxo-1H-pyridazine-5-carboxylate as an off-white solid (17g, 28% over two steps).
1H NMR(400MHz,CDCl3)δ＝11.17(s,1H),7.65(s,1H),4.40(q,2H),1.92-1.85(m,1H),1.38(t,3H),1.02-0.98(m,2H),0.92-0.88(m,2H)。
Step 5. preparation of ethyl 6-cyclopropyl-2- (3, 4-dimethoxyphenyl) -3-oxo-pyridazine-4-carboxylate.
Figure BDA0001826282010000541
To a stirred solution of ethyl 3-cyclopropyl-6-oxo-1H-pyridazine-5-carboxylate (2.00g, 9.61mmol) in dichloromethane (70mL) was added
Figure BDA0001826282010000542
Molecular sieves (0.88g), copper (II) acetate monohydrate (4.01g, 22.1mmol), triethylamine (2.7mL, 19.2mmol) and pyridine (1.6mL, 19.2 mmol). (3, 4-Dimethoxyphenyl) boronic acid (2.6g, 14.4mmol) was then added portionwise over 10 minutes. The reaction mixture was stirred at room temperature for 4 hours with bubbling of compressed air through. After 4 hours, the compressed air was turned off and stirring was continued for a further 16 hours. The reaction mixture was filtered through celite with additional CH2Cl2The residue was washed. The filtrate was washed with 2N aqueous HCl (2X 100mL) and saturated brine solution (100 mL). The organic layer was purified over MgSO4Dried, filtered and concentrated in vacuo to leave a dark yellow gum. Purification was performed by column chromatography eluting with 0-100% EtOAc in isohexane to give ethyl 6-cyclopropyl-2- (3, 4-dimethoxyphenyl) -3-oxo-pyridazine-4-carboxylate (2.46g, 74%) as a bright yellow gum.
1H NMR(400MHz,CDCl3)δ＝7.55(s,1H),7.11(m,2H),6.91(d,1H),4.40(q,2H),3.94(s,3H),3.90(s,3H),1.97(m,1H),1.40(t,3H),1.04(m,2H),0.92(m,2H)。
Step 6.6 preparation of cyclopropyl-2- (3, 4-dimethoxyphenyl) -3-oxo-pyridazine-4-carboxylic acid.
Figure BDA0001826282010000551
To a solution of ethyl 6-cyclopropyl-2- (3, 4-dimethoxyphenyl) -3-oxo-pyridazine-4-carboxylate (2.40g, 6.97mmol) in tetrahydrofuran (50mL) was added water (25mL) followed by lithium hydroxide (0.45g, 10.5 mmol). The resulting solution was stirred at room temperature for 90 minutes. The THF was removed in vacuo and the residual aqueous mixture was diluted with water (25mL) and washed with EtOAc (30 mL). The vigorously stirred aqueous layer was acidified with concentrated HCl solution to pH 1-a yellow precipitate formed. The precipitate was collected by filtration to give 6-cyclopropyl-2- (3, 4-dimethoxyphenyl) -3-oxo-pyridazine-4-carboxylic acid (1.78g, 81%) as a yellow solid.
1H NMR(400MHz,CDCl3)δ＝14.10(br.s,1H),8.06(s,1H),7.14(m,1H),7.10(m,1H),6.97(d,1H),3.95(s,3H),3.90(s,3H),2.10(m,1H),1.15(m,2H),1.00(m,2H)。
Step 7.6 preparation of- [ 6-cyclopropyl-2- (3, 4-dimethoxyphenyl) -3-oxo-pyridazine-4-carbonyl ] -2,2,4, 4-tetramethyl-cyclohexane-1, 3, 5-trione (Compound 1.11).
Figure BDA0001826282010000552
To a solution of 6-cyclopropyl-2- (3, 4-dimethoxyphenyl) -3-oxo-pyridazine-4-carboxylic acid (1.00g, 3.16mmol) in dichloromethane (anhydrous, 20mL) in a 100mL three-necked round-bottomed flask was added N, N-dimethylformamide (anhydrous, 0.012mL, 0.158mmol) followed by dropwise addition of oxalyl chloride (0.29mL, 3.32mmol) under a nitrogen atmosphere and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was cooled to 0 ℃ (salt/ice bath) and triethylamine (1.77mL, 12.7mmol) was added dropwise over 15 minutes, then stirred at 0 ℃ for 5 minutes, then dissolved in a minimum amount of CH added dropwise over 15 minutes2Cl22,2,4, 4-tetramethylcyclohexane-1, 3, 5-trione (0.58g, 3.17mmol) in (1). The resulting solution was stirred at 0 ℃ for 5 minutes and then at room temperature for 1 hour. The reaction mixture was cooled to 0 ℃ and triethylamine (1.77mL, 12.7mmol) was added dropwise over 10 minutes followed by acetone cyanohydrin (0.044mL, 0.475 mmol). The reaction mixture was stirred at 0 ℃ for 5 minutes and then heated at reflux (40 ℃) for 90 minutes. The reaction mixture was allowed to cool to room temperature, filtered and maintained at vacuumThe filtrate was concentrated in air. Purification by column chromatography with 20:8:4:4:1 toluene: dioxane: EtOH: Et3N water to obtain the triethylamine salt of the desired compound. The crude oil was dissolved in MeOH and loaded onto a solid phase extraction SAX column. The column was washed with 3 column volumes of MeOH, and then the desired product was liberated with 1% formic acid in MeOH, concentrated in vacuo to give 6- [ 6-cyclopropyl-2- (3, 4-dimethoxyphenyl) -3-oxo-pyridazine-4-carbonyl as an orange extruded foam]2,2,4, 4-tetramethyl-cyclohexane-1, 3, 5-trione (0.31g, 20%).
1H NMR(400MHz,CDCl3)δ＝7.13(s,1H),7.12-7.06(m,2H),6.91(d,1H),3.91(s,3H),3.88(s,3H),2.00-1.92(m,1H),1.52(br.s,6H),1.40(br.s,6H),1.05-0.98(m,2H),0.98-0.91(m,2H)。
Preparation example 2: preparation of 2- [ 6-cyclopropyl-2- (3, 4-dimethoxyphenyl) -3-oxo-pyridazine-4-carbonyl ] -5-methyl-cyclohexane-1, 3-dione (compound 1.8 (see Table C1)).
Figure BDA0001826282010000561
6-cyclopropyl-2- (3, 4-dimethoxyphenyl) -3-oxo-pyridazine-4-carboxylic acid (1.00g, 3.16mmol) was added to anhydrous DCM (20mL) and one drop of anhydrous DMF was added thereto. Oxalyl chloride (0.35mL, 4.11mmol) was then added dropwise to the mixture and stirred for 1 h. The reaction mixture was concentrated under reduced pressure under a nitrogen atmosphere. The crude reaction mass was then dissolved in anhydrous DCM (15mL), activated molecular sieve was added and the reaction mixture was cooled in an ice salt bath. Triethylamine (1.23mL, 9.48mmol) was then added dropwise to the reaction mixture over 15 minutes. 5-methyl-1, 3-cyclohexanedione (479mg, 3.79mmol) in DCM (10mL) was then added dropwise to the reaction mixture. Stirred at room temperature for 1 hour. Triethylamine (1.23mL, 9.48mmol) and acetone cyanohydrin (0.22mL, 2.37mmol) were then added and the reaction stirred for 2.5 h. The crude product was diluted with DCM and washed with 1N HCl. Purification by column chromatography with 20:8:4:4:1 toluene: dioxane: EtOH: Et3Mixed solvent of N and waterThe system was eluted to give the triethylamine salt of the desired compound as a brown gum. To which was added water (25mL) and CH2Cl2(25mL) and acidified to pH 1 with 2M HCl. The mixture was stirred for 5 minutes, then the phases were separated by a phase separation column and CH was added2Cl2And (6) washing. The organic phase is concentrated to give the desired product, 2- [ 6-cyclopropyl-2- (3, 4-dimethoxyphenyl) -3-oxo-pyridazine-4-carbonyl as a solid]-5-methyl-cyclohexane-1, 3-dione (850mg, 2.00mmol, 63%).
1H NMR(400MHz,CDCl3)δ＝7.14-7.10(2H,m),6.98(1H,s),6.89(1H,d),3.89(3H,s),3.87(3H,s),2.75-2.71(1H,m),2.53-2.39(2H,m),2.32-2.26(1H,m),2.18-2.12(1H,m),1.97-1.90(1H,m),1.08(3H,d),0.99-0.95(2H,m),0.93-0.87(2H,m)。
Preparation example 3: preparation of 2- [2- (3, 4-dimethoxyphenyl) -6-methyl-3-oxo-pyridazine-4-carbonyl ] cyclohexane-1, 3-dione (Compound 1.3 (see Table C1)).
Step 1.1 preparation of bromopropane-2-one.
Figure BDA0001826282010000571
Acetone (150g, 2.58mol), water (480mL) and glacial acetic acid (90mL) were stirred in a two-necked round bottom flask and heated to reflux (75 deg.C). Bromine (73.2mL, 2.84mol) was added portionwise to the solution. The reaction mixture was heated at 75 ℃ until it became colorless. It was then cooled to 0 ℃ (ice bath) and water (100mL) was added, followed by sufficient Na2CO3Until it is no longer acidic. The reaction mixture was transferred to a separatory funnel and the bottom organic layer was separated over Na2SO4Dried and filtered to give 1-bromopropan-2-one (99.0g, 28%).
1H NMR(CDCl3,400MHz)δ＝3.23(s,2H),1.67-1.72(m,3H)。
Step 2. preparation of diethyl 2-acetonyl malonate.
Figure BDA0001826282010000581
1-Bromopropan-2-one (90g, 0.66mol) was dissolved in acetone (740mL) and diethyl malonate (126mL, 0.79mol), K, were added under nitrogen2CO3(136g, 0.99mol) and KI (3.27g, 19.7mmol) were added to the stirred solution. The reaction mixture was heated at reflux for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated in vacuo. The crude material was dissolved in EtOAc and washed with water, followed by brine. Subjecting the organic layer to Na2SO4Dried, filtered and concentrated in vacuo to give a liquid. Subjecting the crude material to column chromatography on CH2Cl20-5% MeOH in to give diethyl 2-acetonylmalonate as a light yellow oil (80.0g, 56%).
1H NMR(CDCl3,400MHz)δ＝4.21-4.04(m,4H),3.78(t,1H),2.99(d,2H),2.20-2.06(m,3H),1.27-1.13ppm(m,6H)。
Step 3. preparation of ethyl 3-methyl-6-oxo-4, 5-dihydro-1H-pyridazine-5-carboxylate.
Figure BDA0001826282010000582
Diethyl 2-acetonylmalonate (80g, 370mmol) was dissolved in absolute ethanol (175mL) and cooled to 0 ℃. To the stirred solution was added hydrazine hydrate (20.4mL,407mmol) dropwise. The mixture was allowed to warm to room temperature and stirred for 16 hours. The reaction mixture was concentrated in vacuo and the resulting crude ethyl 3-methyl-6-oxo-4, 5-dihydro-1H-pyridazine-5-carboxylate was used in the next step without further purification (61.0g crude, 90%).
Step 4. preparation of ethyl 3-methyl-6-oxo-1H-pyridazine-5-carboxylate.
Figure BDA0001826282010000591
A solution of bromine (17mL, 662mmol) in acetic acid (140mL) was added portionwise to a stirred solution of ethyl 3-methyl-6-oxo-4, 5-dihydro-1H-pyridazine-5-carboxylate (61g crude, 331mmol) in acetic acid (1250 mL). The reaction mixture was stirred at room temperature for 1 hour, then concentrated in vacuo. The crude material was dissolved in EtOAc and the solution was washed with water, followed by brine, over Na2SO4Dried, filtered and concentrated in vacuo. Subjecting the crude material to column chromatography on CH2Cl2Purification was performed eluting with 0-5% MeOH in to give ethyl 3-methyl-6-oxo-1H-pyridazine-5-carboxylate (22.0g, 37%) as an off-white solid.
1H NMR(CDCl3,400MHz)δ＝7.71(s,1H),4.40(q,2H),2.39(s,3H),1.39(t,3H)。
Step 5. preparation of ethyl 2- (3, 4-dimethoxyphenyl) -6-methyl-3-oxo-pyridazine-4-carboxylate.
Figure BDA0001826282010000592
To a solution of ethyl 3-methyl-6-oxo-1H-pyridazine-5-carboxylate (5.0g,27.4mmol) in dichloromethane (200mL) was added copper (II) acetate monohydrate (12.6g, 63.1mmol) and,
Figure BDA0001826282010000593
Molecular sieves, pyridine (4.4mL,54.9mmol) and triethylamine (7.7mL,54.9 mmol). To the stirred suspension was added (3, 4-dimethoxyphenyl) boronic acid (7.0g, 38.4mmol) portionwise over 5 min and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was filtered through celite with additional CH2Cl2The residue was washed. The filtrate was washed with 2N aqueous HCl (2X 200mL) over MgSO4Dried, filtered and concentrated in vacuo. Purification was by column chromatography eluting with 20% -100% EtOAc in isohexane to give ethyl 2- (3, 4-dimethoxyphenyl) -6-methyl-3-oxo-pyridazine-4-carboxylate (5.10g, 58%) as a pale yellow solid.
1H NMR(400MHz,CDCl3)δ＝7.66(s,1H),7.11(br.s,2H),6.93(d,1H),4.41(q,2H),3.92(s,3H),3.90(s,3H),2.44(s,3H),1.39(t,3H)。
Step 6.2- (3, 4-dimethoxyphenyl) -6-methyl-3-oxo-pyridazine-4-carboxylic acid preparation.
Figure BDA0001826282010000601
To a solution of ethyl 2- (3, 4-dimethoxyphenyl) -6-methyl-3-oxo-pyridazine-4-carboxylate (12.0g, 37.7mmol) in tetrahydrofuran (200mL) cooled to 0 ℃ (ice bath) was added a solution of lithium hydroxide monohydrate (2.37g, 56.5mmol) in water (100 mL). The reaction mixture was allowed to warm to room temperature and stirred for 30 minutes. THF was removed in vacuo, and the aqueous mixture was washed with CH2Cl2Wash (3 × 40 mL). The aqueous solution was cooled to 0 ℃ and concentrated HCl solution was added while stirring until a pH of 1 was reached. A bright yellow solid precipitated during the process. The solid was collected by filtration. Dissolving the solid in CH2Cl2And the solution is passed over MgSO4Dried, filtered and concentrated in vacuo to give 2- (3, 4-dimethoxyphenyl) -6-methyl-3-oxo-pyridazine-4-carboxylic acid (9.5g, 87%) as a bright yellow solid.
1H NMR(400MHz,CDCl3)δ＝14.01(br.s,1H),8.18(s,1H),7.16(d,1H),7.08(br.s,1H),6.98(d,1H),3.94(app.d,6H),2.55(s,3H)。
Step 7.2- [2- (3, 4-dimethoxyphenyl) -6-methyl-3-oxo-pyridazine-4-carbonyl ] cyclohexane-1, 3-dione (Compound 1.3) preparation.
Figure BDA0001826282010000611
To a solution of 2- (3, 4-dimethoxyphenyl) -6-methyl-3-oxo-pyridazine-4-carboxylic acid (1.00g, 3.44mmol) in dichloromethane (anhydrous, 13mL) was added 3 drops of N, N-dimethylformamide (anhydrous) followed by the dropwise addition of oxalyl chloride (0.33mL, 3.79 mmol). The reaction mixture is added inStirred at room temperature for 16 hours. DMF (1 drop) and oxalyl chloride (0.1mL) were added and stirring was continued at room temperature for 1 hour. To a cooled (0 deg.C (ice bath)) solution of cyclohexane-1, 3-dione (0.41g, 3.62mmol) in dichloromethane (anhydrous, 7.0mL) was added triethylamine (1.44mL, 10.3 mmol). The acid chloride solution was then added to the cyclohexane-1, 3-dione-triethylamine solution by means of a syringe pump over a period of 10 minutes (70mL/h) and the reaction mixture was stirred at 0 ℃ for a further 5 minutes. Additional triethylamine (0.48mL, 3.45mmol) was added followed by acetone cyanohydrin (as anhydrous CH)2Cl2Stock solution of (1) (10 mol%, 0.34 mmol). The reaction flask was transferred to a preheated oil bath and heated with stirring at reflux (40 ℃) for 6 hours, and then stirred at room temperature for another 16 hours. The reaction mixture was concentrated in vacuo to give a black residue. Purification by column chromatography with 20:8:4:4:1 toluene: dioxane: EtOH: Et3N water to give the triethylamine salt of the desired compound as a brown gum. To which was added water (25mL) and CH2Cl2(25mL) and acidified to pH 1 with 2M HCl. The mixture was stirred for 5 minutes, then the phases were separated by a phase separation column and CH was added2Cl2And (6) washing. The organic phase was concentrated to give 2- [2- (3, 4-dimethoxyphenyl) -6-methyl-3-oxo-pyridazine-4-carbonyl as an orange foam]Cyclohexane-1, 3-dione (400mg, 30% yield).
1H NMR(400MHz,CDCl3) δ is 16.14(1H, s),7.13(1H, dd),7.09(2H, m),6.92(1H, d),3.90(3H, s),3.89(3H, s),2.73(3H, t),2.46(3H, t),2.41(3H, s),2.04(2H, quintuple).
Preparation example 4.3 preparation of- [2- (3, 4-dimethoxyphenyl) -6-methyl-3-oxo-pyridazine-4-carbonyl ] bicyclo [3.2.1] octane-2, 4-dione (compound 1.1 (see table C1)).
Figure BDA0001826282010000621
DMF (catalyst) and oxalyl chloride (0.6mL) was added to 2- (3, 4-dimethoxyphenyl) -6-methyl-3-oxo-pyridazine-4-carboxylic acid (1.5 g)5.172mmol) in DCM (20 mL). The reaction mixture was stirred at room temperature for 1.5 h. TLC (after quenching with MeOH) showed formation of non-polar spots. The reaction mass was evaporated under N2 atmosphere. DCM (20mL) was added followed by a scoop of molecular sieves. TEA (2.2mL) and bicyclo [3.2.1]]Octane-2, 4-dione (0.86g, 6.2mmol) was added to the acid chloride solution. The reaction mixture was stirred at room temperature for 1 h. Triethylamine (2.2mL) and 25 drops of acetone cyanohydrin were added and stirred for 2 h. The reaction mass was chromatographed at 20:8:4:4:1 toluene: dioxane: EtOH: Et3N water, and acidified by 10% HCl solution and extracted with DCM. The solvent was evaporated to give the crude compound, which was further purified by chromatography with acetone-DCM to give the desired product, 3- [2- (3, 4-dimethoxyphenyl) -6-methyl-3-oxo-pyridazine-4-carbonyl, as a solid]Bicyclo [3.2.1]Octane-2, 4-dione (500mg, 1.22mmol, 24%).
1H NMR(400MHz,CDCl3)δ＝16.19(1H,s),7.16-7.09(3H,m),6.93(1H,d),3.91(6H,s),3.11(1H,t),2.94(1H,t),2.42(3H,s),2.26-2.06(3H,m),2.04-1.98(1H,m),1.83(1H,brm),1.72(1H,dt)。
Biological examples
Seeds of various test species HORVW (Hordeum vulgare-barley), ABUTH (Chrysanthemum coronarium), AMARE (Amaranthus retroflexus) and ECHCG (Echinochloa crusgalli) were sown in standard soil in pots. After 10 days of culture under controlled conditions in the greenhouse (24 ℃/16 ℃, day/night; 14 hours light; 65% humidity), the plants were sprayed with an aqueous spray solution derived from the formulation of industrial grade active ingredient in 0.6ml acetone and 45ml formulation solution containing 10.6% Emulsogen EL (accession number 61791-12-6), 42.2% N-methylpyrrolidone, 42.2% dipropylene glycol monomethyl ether (CAS RN 34590-94-8) and 0.2% X-77(CAS RN 11097-66-8).
The test plants were then grown under controlled conditions in the greenhouse (at 24 ℃/16 ℃, day/night; 14 hour light; 65% humidity) and watered twice daily. After 14 days, the tests were evaluated (100 ═ damage complete to the plant; 0 ═ no damage to the plant).
TABLE B1
Figure BDA0001826282010000631
These comparative results show that the dimethoxyphenyl-substituted pyridazinone compounds of the present invention surprisingly cause less damage to crop plants (barley-HORVW) while maintaining good control of representative weed species (ECHCG, ABUTH, AMARE) compared to the equivalent monomethoxyphenyl compounds specifically disclosed in WO 2012/136703.
TABLE B2
Figure BDA0001826282010000641
These results show that the compounds of the invention have hardly any damage when applied to crop plants (barley-HORVW), but still provide good control of representative weed species (ECHCG, ABUTH, AMARE).

Claims (13)

1. A compound having the formula (I):
Figure FDA0002965873830000011
or an agronomically acceptable salt thereof, or a pharmaceutically acceptable salt thereof,
wherein
R1Is C1-C6Alkyl-or C3-C6Cycloalkyl-;
A1is (CR)eRf)；
Ra、Rb、Rc、Rd、ReAnd RfEach independently selected from the group consisting of: hydrogen and C1-C4Alkyl-, wherein RaAnd RcMay be taken together to form C1-C3An alkylene chain.
2. The compound of claim 1, wherein R1Is methyl or cyclopropyl-.
3. The compound of claim 1, wherein a1Is CReRfAnd R iseAnd RfIs hydrogen.
4. The compound of claim 1, wherein Ra、Rb、RcAnd RdIs hydrogen.
5. The compound of claim 1, wherein RaAnd RcTogether form-CH2-CH2-chain and RbAnd RdIs hydrogen.
6. A compound according to any one of claims 1 to 5 in the form of an agrochemically acceptable salt, wherein the agrochemically acceptable salt is selected from the group consisting of: aluminum, calcium, cobalt, copper, iron, magnesium, potassium, sodium, and zinc.
7. A herbicidal composition comprising a compound according to any one of claims 1 to 6 and an agriculturally acceptable formulation adjuvant.
8. The herbicidal composition of claim 7, further comprising at least one additional pesticide.
9. A herbicidal composition according to claim 8, wherein the additional pesticide is a herbicide or herbicide safener.
10. A method of controlling weeds at a locus, the method comprising applying to the locus a weed controlling amount of a composition according to any one of claims 7 to 9.
11. A compound having the formula (II)
Figure FDA0002965873830000021
Wherein
R1Is as defined in claim 1, and
R2selected from the group consisting of: halogen, -OH, C1-C6Alkoxy-, aryloxy and N-linked imidazolyl.
12. A method of producing a compound according to claim 1 having formula (I), the method comprising: (i) reacting a compound having formula (IIc):
Figure FDA0002965873830000031
wherein R is1Is as defined for formula (I) according to claim 1, and LG is a suitable leaving group, is reacted with a diketone of formula (III)
Figure FDA0002965873830000032
Wherein A is1、Ra、Rb、Rc、RdEach as defined in claim 1, and
(ii) the resulting product is rearranged into a compound having formula (I).
13. Use of a compound of formula (I) as defined in claim 1 as a herbicide.
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WO2023040686A1 (en) * 2021-09-16 2023-03-23 江苏中旗科技股份有限公司 Pyridazinone compound, preparation method, herbicide composition and use thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4411691A (en) * 1978-02-25 1983-10-25 Basf Aktiengesellschaft 1-Substituted phenyl-pyridazone herbicides
CN1192208A (en) * 1995-06-06 1998-09-02 拜尔公司 Phenylpyridazinones
WO2012136703A1 (en) * 2011-04-08 2012-10-11 Syngenta Limited Herbicidal compounds
CN103664795A (en) * 2012-09-06 2014-03-26 华东理工大学 Pyridazine ketone compound and use thereof
CN103874688A (en) * 2011-10-04 2014-06-18 先正达有限公司 Herbicidal pyridazinone derivatives

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB797905A (en) 1958-08-16 1958-07-09 Walter Gfoell A combined vehicle pneumatic tyre valve cap and pressure gauge
DE4423934A1 (en) 1993-09-02 1995-03-09 Basf Ag 3(2H)-Pyridazinone derivatives, their preparation and their use
WO1999052878A1 (en) * 1998-04-09 1999-10-21 Bayer Aktiengesellschaft Substituted phenyl pyridazinones
ES2575396T3 (en) 2012-03-20 2016-06-28 Syngenta Limited Herbicidal compounds

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4411691A (en) * 1978-02-25 1983-10-25 Basf Aktiengesellschaft 1-Substituted phenyl-pyridazone herbicides
CN1192208A (en) * 1995-06-06 1998-09-02 拜尔公司 Phenylpyridazinones
WO2012136703A1 (en) * 2011-04-08 2012-10-11 Syngenta Limited Herbicidal compounds
CN103874688A (en) * 2011-10-04 2014-06-18 先正达有限公司 Herbicidal pyridazinone derivatives
CN103664795A (en) * 2012-09-06 2014-03-26 华东理工大学 Pyridazine ketone compound and use thereof

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